Peanut allergy burden survey: Factors associated with health‐related quality of life in adolescents

Abstract Background Patients with peanut allergy (PA) experience significant burden of illness, which impacts health‐related quality of life (HRQoL), particularly in adolescence. There is a paucity of research evaluating drivers of HRQoL scores. Methods A prospective, online survey of adolescents with self‐reported, provider‐diagnosed PA completed from November 2018 to January 2019 was used to explore drivers of the real‐world impact of PA on HRQoL using the Pediatric Quality of Life Inventory 4.0 (PedsQL) and other measures. Univariate and multivariate analyses were used to identify potential factors associated with PedsQL scores and to understand the level of association. Results A total of 102 adolescents were included. The final model included 10 variables: race, reported strict peanut avoidance, satisfaction with prophylaxis, moderate‐to‐severe reaction within the past 12 months, touching peanut as cause of most severe reaction, fear of reaction, age, gender, comorbidities, and daily life limitations. In total, three items were shown to be strong predictors of the PedsQL total score including cause of severe reaction was touching peanut (yes), level of agreement with avoiding peanut (completely agree), and satisfaction with prophylaxis (not very much/not at all). Conclusions There is substantial heterogeneity in the impact of the burden of PA on PedsQL scores across patients. This indicates the importance of shared and individualized decision making for PA management to optimize outcomes and improve HRQoL.

costs, and even mortality. 2 The Peanut Allergy Burden Study (PABS) was a large survey study that assessed the real-world burden of peanut allergies on patients and caregivers in the US. In an analysis of PABS, McCann et al. reported frequent healthcare resource utilization in children, adolescents, and adults including regular and unscheduled allergist appointments, general practitioner appointments, over the counter medication usage, and epinephrine autoinjector usage as well as substantial loss in productivity. Additionally, in the past 12 months, 56.9%-59.9% of adolescent and adult patients and caregivers reported at least one PA-related emergency or urgent care visit, 36.3%-47.4% reported an overnight hospital admission, 37.2%-52.3% reported intravenous (IV) epinephrine use, and 26.5%-39.8% reported intubation in the past 12 months. 4 While PA represents a societal burden, it also represents a burden on the individual due to dietary restrictions, precautions on reading food labels and eating at restaurants, exposure during travel, work, or school, and an emotional toll that may affect the patient or caregiver's health-related quality of life (HRQoL). 2 Published literature have reported significant impacts of PA on HRQoL measures in patients, parents, and siblings including impairment in the familialsocial dimension in peanut allergic children and adolescents. 5,6 In an assessment of HRQoL from PABS data, Nowak-Wegrzyn reported that PA patients and caregivers had worse HRQoL when compared to healthy populations in all domains of the survey and, when compared to a chronically ill population, reported worse overall HRQoL, psychosocial, emotional, and social functioning. Specifically, adolescents were reported experiencing a greater impact on overall healthrelated HRQoL than adults due to the social burden of allergen avoidance and dietary restriction. 7 Despite these results, there is a paucity of HRQoL data and studies specifically evaluating the experience of adolescents with PA.
The goal of this analysis was to utilize PABS data to identify potential predictors of Pediatric Quality of Life Inventory 4.0 (PedsQL) scores in adolescents with PA to add to the literature base and improve management opportunities for these patients.

| Survey study design
PABS was a cross-sectional survey employed to examine the realworld impact of PA in peanut-allergic adolescents and adults, as well as caregivers of peanut-allergic children. This study is a sub-analysis of the peanut-allergic adolescent sample to identify potential real-world predictors of PedsQL scores in this population. The study was reviewed and approved by the Solutions Institutional Review Board (IRB). 8

| Data collection and procedures
This was a prospective, online survey of adolescents with selfreported, provider-diagnosed PA. Participants were recruited through emails sent by Lightspeed, a market research company with a US panel of 1.3 million individuals, inviting them to participate in the survey. A screening questionnaire was used to determine eligibility with the inclusion and exclusion criteria described below.
Eligible participants who completed the screening questions and met the inclusion criteria were invited to complete the online survey.
Participants gave informed consent to be in the overall research panel and to voluntarily opt-in to complete this survey. A caregiver's consent was also required for the adolescent to participate. HRQoL measure) will not be described in the current manuscript. 4,7 Study participants were compensated with "award points" that could be redeemed for gift certificates, merchandise, or cash.

| Participants
PABS recruited three samples consisting of peanut-allergic adolescents, peanut-allergic adults, and caregivers of peanut-allergic children. Inclusion criteria for each sample were previously published. 4,7 Since the current study aimed to identify potential factors associated with PedsQL scores in peanut-allergic adolescents, only one sample was used in this analysis. Eligible peanut-allergic adolescents met the following inclusion criteria: (1) between 13 and 17 years old; (2) selfreported physician-diagnosed PA; (3) use of medication or medical care to treat a PA reaction or patient/caregiver always carries emergency medication; (4) "agree completely" or "very much" that they avoid being around peanuts; and (5) English-speaking US resident. Participating in a clinical study for PA treatment was allowed.
For peanut-allergic adolescents, recruitment quotas were set to ensure an approximate 50:50 male to female ratio. After gender quota was met, potential participants who met the inclusion criteria were excluded. The response rate was 97% after inclusion and exclusion criteria were applied.

| Baseline demographics and medical history
Demographic information collected included age, gender, and race/ ethnicity. Medical history questions pertained to the patient's age at the first-ever allergic reaction to peanuts, age at which PA was diagnosed, method of diagnosis, severity of PA reactions experienced in the past 12 months and over their lifetime, symptoms during the last allergic reaction, and the worst lifetime allergic reaction, treatment history, and satisfaction with treatment.

| Healthcare resource utilization
PABS assessed PA-specific healthcare resource utilization through questions beginning with the prompt of: "Thinking about your medical care and allergic reactions due to peanut." Participating peanutallergic adolescents were asked to report PA-related healthcare resource utilization in the previous 12 months and over their lifetime through a variety of prompts.

| PedsQL
The PedsQL questionnaire administered to peanut-allergic adolescents is a validated, 23-item self-report instrument that measures HRQoL with developmentally appropriate self-report forms for children (age 8-12) and adolescents (age [13][14][15][16][17][18], and proxy-report forms for parents HRQoL in healthy children and adolescents, as well as those with acute and chronic health conditions. 9 Table 2).

| Analytic model
In total, three items were shown to be strong predictors of the PedsQL total score including cause of severe reaction was touching peanut (yes), level of agreement with avoiding peanut (completely agree), and satisfaction with prophylaxis (not very much/not at all). MCCANN ET AL.  Table 2.

Identifying drivers of HRQoL survey scores is imperative in trans-
forming reported responses to actionable data that supports clinical decision making. In this study, survey responses to the PedsQL were strongly driven by three factors relating to the cause of severe reactions, the level of avoidance of peanuts, and dissatisfaction with PA prophylaxis. However, when the model was applied to individual patient scores, more heterogeneity in the drivers of results were observed, highlighting the complexity of successful management of adolescents with PA. These results are aligned with previous literature reporting a wide variety of HRQoL score drivers among different patient age groups, ethnicities, and countries of origin. 12,13 In a previous publication of PedsQL scores in adolescents in    25 Similarly, treatment with OIT has been associated with improved HRQoL in both patients and caregivers. 26,27 In the present reported study, results showed a correlation between lack of satisfaction with current therapy (i.e., avoidance) and poorer HRQoL, and thus it stands to reason that novel therapies may improve HRQoL. Understanding the potential HRQoL outcomes associated with emerging PA therapies will help describe the full impact of these management strategies and inform shared provider, patient, and/or caregiver decision making.

| Limitations
This survey relied on self-reported measures, which may introduce several forms of bias into the results. Given that inclusion criteria specified the enrollment of only English-speaking US residents, the results might have been limited by the overall diversity in the sample pool. However, it is notable that the sample was racially diverse, with almost 40% of patients being non-White. To our knowledge, this is the first study to capture such a diverse patient population in this space. Next, because patients had to require either medication or medical care because of a peanut reaction, results may not represent all individuals with PA, particularly those where avoidance of peanuts is a successful strategy or who may not be sensitive to very small amounts of peanut. Finally, there are specific instruments that exist evaluating food allergy in adolescents, such as the FAQL-teen, 28 but we utilized the PedsQL instrument as an instrument that would enable a comparison of the responses of adolescents with PA to those of their peers without PA.